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Chimeric antigen receptor and natural killer cells expressing same

a technology of chimeric antigen receptor and natural killer cells, which is applied in the direction of genetically modified cells, fusions for specific cell targeting, antibody medical ingredients, etc., can solve the problems of difficult use of nk cells, unreported ox40 ligand for enhancing the anticancer activity of nk cells, and unreported ox40 ligand for chimeric antigen receptor, etc., to achieve excellent nk cell activation efficiency and excellent cytotoxicity

Inactive Publication Date: 2019-11-07
GC CELL CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is a chimeric antigen receptor that can be used to activate natural killer (NK) cells, which are a type of immune cell. The receptor can be used with different cancer-target antibodies and is effective in treating various cancer types. The receptor is also highly efficient in targeting cancer cells and can be used in immune cell therapy.

Problems solved by technology

However, due to difficulties in ex vivo cell expansion and differences in activities of NK cells in individual patients, it is difficult to use the NK cells.
However, a role of OX40 ligand in enhancement of anticancer activity of NK cells is not well known, and an attempt to use the OX40 ligand for the chimeric antigen receptor is still not yet reported.

Method used

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  • Chimeric antigen receptor and natural killer cells expressing same
  • Chimeric antigen receptor and natural killer cells expressing same
  • Chimeric antigen receptor and natural killer cells expressing same

Examples

Experimental program
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Effect test

example 2

t of Cytotoxicity of NK92MI Cells Expressing OX40 Ligand (CD252)-Containing Chimeric Antigen Receptor (CAR) Against CD20-Positive Lymphoma Cells

[0155]Transduction and Expression of Chimeric Antigen Receptor Containing CD16V Associated with the Co-Stimulating Motif

[0156]V158 variant (polymorphism) of FCRG3A (CD16) is a high affinity immunoglobulin Fc receptor and is considered to exhibit good effects in antibody treatment. The present inventors have prepared the V158 variant of FCRG3A (CD16) and combined the prepared variant with: the hinge and transmembrane domains of CD8α; a T cell stimulatory molecule, that is, CD3ζ; and intracellular domains of different costimulatory molecules such as CD28, 4-1BB, OX-40 and OX-40 ligand in various combinations thereof (Table 1). The prepared CD16V-containing chimeric antigen receptors (e.g., CD16V-Z CAR (1st generation), CD16V-28Z CAR (2nd generation), CD16V-BBZ CAR (2nd generation), CD16V-OX40Z CAR (2nd generation) or CD16V-28OX40LZ CAR (3rd ge...

example 3

t of Cytotoxicity of NK92MI Cells Expressing OX40 Ligand (CD252)-Containing NKG2D Chimeric Antigen Receptor (NKG2D-CAR) on Human Breast Cancer Cells and Lung Cancer Cells

[0175]Transduction and Expression of a Chimeric Antigen Receptor Including NKG2D Associated with Co-Stimulatory Motif

[0176]The present inventors synthesized a human NKG2D gene and combined the same with diverse combinations of: hinge and transmembrane domains of CD8α; and intracellular domains of T-cell stimulatory molecules CD3ζ and cofactors including CD28, 4-1BB, OX-40 and OX-40 ligand to significantly enhance activity of T or NK cells (Table 3). Such NKG2D CAR constructs were expressed in NK92MI cells using a lentiviral vector. The present inventors have identified surface expression of each NKG2D CAR in NK92MI cells by means of detection of human NKG2D using a monoclonal mouse anti-human antibody. By repetitive experiments involving flow cytometric analysis, it was demonstrated that CARs were transduced with 70...

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Abstract

The present invention provides a chimeric antigen receptor and natural killer cells expressing the same, and particularly, a chimeric antigen receptor (CAR) which includes an intracellular signaling domain including the whole or a portion of an OX40 ligand (CD252), thereby having excellent effects of increasing anticancer activity of immune cells, and immune cells expressing the same.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a National Stage of International Application No. PCT / KR2017 / 015635 filed Dec. 28, 2017, claiming priority based on Korean Patent Application No. 10-2016-0181119 filed Dec. 28, 2016.TECHNICAL FIELD[0002]The present invention relates to a chimeric antigen receptor and natural killer cells expressing the same.BACKGROUND ART[0003]Human natural killer cells (NK cells) play an important role in innate immune defense against malignant lymphoma cells, and thus may be suitable for adoptive immune therapy (i.e., adoptive cellular immunotherapy). However, due to difficulties in ex vivo cell expansion and differences in activities of NK cells in individual patients, it is difficult to use the NK cells.[0004]In a field of immune cell therapy using T cells, that is, T cell therapy field, a chimeric antigen receptor for treatment of autoimmune cells has been developed. The chimeric antigen receptor has been known to help activation ...

Claims

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Application Information

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IPC IPC(8): A61K35/17C07K16/28C07K14/725
CPCC07K2317/73C07K2319/03C07K16/2818C07K16/2815A61K35/17C07K2317/622C07K16/2851C07K14/7051C07K16/283C07K2319/33C07K14/705C07K16/00C07K14/70596C07K14/70575A61P35/00C07K14/70578C07K14/70517C07K14/70521C12N5/0646C12N2510/00A61K39/4613A61K39/4631A61K39/464429A61K2239/55A61K2239/22A61K2239/49A61K2239/48A61K39/464424
Inventor HWANG, YU KYEONGCHO, SUNG YOOWON, SUNG YONGLIM, HO YONGHER, JUNG HYUNJUNG, MI YOUNGKIM, HYUN AHGWON, SU HYUNLEE, EUN SOLKIM, HAN SOL
Owner GC CELL CORP
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